DISORDERS OF THE THYROID GLAND SIGNS, SYMPTOMS, & TREATMENT ENDOCRINE SYSTEM AT A GLANCE OBJECTIVES ANATOMY OF THE THYROID

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OBJECTIVES DISORDERS OF THE THYROID GLAND SIGNS, SYMPTOMS, & TREATMENT Stephanie Blackburn, MHS, MLS(ASCP) CM LSU Health Shreveport Clinical Laboratory Science

Assess symptoms, lab values, and treatment associated with various thyroid conditions.

1 OBJECTIVES DISORDERS OF THE THYROID GLAND SIGNS, SYMPTOMS, & TREATMENT Stephanie Blackburn, MHS, MLS(ASCP) CM LSU Health Shreveport Clinical Laboratory Science Program Discuss the synthesis and action of thyroid hormones. Differentiate various thyroid abnormalities. Assess symptoms, lab values, and treatment associated with various thyroid conditions. 2 ENDOCRINE SYSTEM AT A GLANCE Growth & development Metabolism Network of glands Secrete hormones Regulate internal processes Response to stimuli Homeostasis Reproduction 3 4 ANATOMY OF THE THYROID Butterfly-shaped gland Lies in front of trachea, below larynx Two lobes connected by isthmus 5 6 1

The thyroid releases hormones that control metabolism the

hormones Heart rate CNS Muscle strength Weight 7 8 THYROID

Thyrotropin Releasing Hormone TSH Stimulating Hormone

T3 T4 N T3 T4 N 9 10 NEGATIVE FEEDBACK Hypothalamus N TRH

Dietary iodine Critical first step in synthesis Absorbed by

THYROID HORMONES produced Iodine deficiency leads to

2 The thyroid releases hormones that control metabolism the way the body uses energy Menstrual cycle Body temp Breathing hormones Heart rate CNS Muscle strength Weight 7 8 THYROID PHYSIOLOGY Hypothalamus Posterior pituitary gland TRH Thyrotropin Releasing Hormone TSH Stimulating Hormone NEGATIVE FEEDBACK Hypothalamus TRH Pituitary gland TSH gland T3 T4 N T3 T4 N 9 10 NEGATIVE FEEDBACK Hypothalamus N TRH Pituitary gland TSH gland T3 T4 N SYNTHESIS OF T 3 AND T 4 Dietary iodine Critical first step in synthesis Absorbed by thyroid cells à combine with tyrosine (in presence of TPO) à THYROID HORMONES produced Iodine deficiency leads to hypothyroidism & cretinism Recommended intake: 150 µg/dl adults µg/dl children

THYROID HORMONES T 4 à thyroxine Deiodination of T 4 to form T 3 T 3 à triiodothyronine Strongest & most potent T 4 80% T 3 20% THYROID HORMONES T3 (99.6%) and T4 (99.

first assessed Normal 0.5-5 µu/ml If TSH is abnormal Free T 4 Normal 0.8-2.

3 THYROID HORMONES T 4 à thyroxine Deiodination of T 4 to form T 3 T 3 à triiodothyronine Strongest & most potent T 4 80% T 3 20% THYROID HORMONES T3 (99.6%) and T4 (99.97%) bound to proteins in circulation binding globulin (TBG) -binding pre-albumin(tbpa) Transthyretin (TTR) Albumin Only free T3 and T4 (FT3, FT4) are metabolically active LAB EVALUATION TSH first assessed Normal µu/ml If TSH is abnormal Free T 4 Normal ng/dl THYROID SCANNING Nuclear imaging Inject radioactive iodine Checks thyroid function or abnormalities (lumps, inflammation, cancer) Ultrasound Detects thyroid nodules, cysts, or tumors Useful to evaluate recurrent thyroid cancer THYROID DISEASE THYROID DISEASE Affects more than12% of U.S. population ~20 million Americans ~60% unaware Affects 1 in 8 women Women 5x more likely to be affected than men 18 3

THYROID DISEASE THYROID DISORDERS Often traced to on of the following: Too much thyroid hormone Too little thyroid hormone Abnormal growth of thyroid Goiters nodules itis Nodules within the

of thyroid hormones or malignancy 21 22 CAUSE

4 THYROID DISEASE THYROID DISORDERS Often traced to on of the following: Too much thyroid hormone Too little thyroid hormone Abnormal growth of thyroid Goiters nodules itis Nodules within the thyroid cancer cancer THYROID DISORDERS GOITER Enlarged thyroid gland Entire gland Goiters nodules itis OR Multiple nodules cancer Non-toxic goiter Not associated with overproduction of thyroid hormones or malignancy CAUSES OF GOITERS: Iodine deficiency Rare in U.S. Increased thyroid stimulating hormone (TSH) Enlargement takes several years Grave s disease & Hashimoto s disease nodules itis cancer GOITER Swollen neck Mass may compress trachea & esophagus Coughing Wake up with feeling of inability to breathe Sensation that food is stuck in throat

TREATMENT FOR GOITERS Depends on cause of goiter Asymptomatic à no treatment Hashimoto s à treat with thyroid hormone Grave s à treat with radioactive iodine If very large or therapy fails à surgical

hormone cancer PRIMARY hypothyroidism SECONDARY hypothyroidism TERTIARY hypothyroidism Rare 27 28 PRIMARY HYPOTHYROIDISM CAUSES - PRIMARY HYPOTHYROIDISM ~10% women have some degree of hypothyroidism

5 TREATMENT FOR GOITERS Depends on cause of goiter Asymptomatic à no treatment Hashimoto s à treat with thyroid hormone Grave s à treat with radioactive iodine If very large or therapy fails à surgical removal necessary INDICATIONS FOR SURGERY Compression of trachea or esophagus Malignancy Cosmetic purposes THYROID DISORDERS HYPOTHYROIDISM Goiters nodules itis Insufficient levels thyroid hormone cancer PRIMARY hypothyroidism SECONDARY hypothyroidism TERTIARY hypothyroidism Rare PRIMARY HYPOTHYROIDISM CAUSES - PRIMARY HYPOTHYROIDISM ~10% women have some degree of hypothyroidism Women 4x more likely than men Prevalence increases with age Mean age at diagnosis is 60 yr Millions are asymptomatic Iodine deficiency (most common worldwide) Autoimmune disease Hashimoto s Iatrogenic Treatment for hyperthyroidism Congenital Trauma Radiation exposure Infections Drugs

6 SYMPTOMS PRIMARY HYPOTHYROIDISM LAB EVALUATION Fatigue Weakness Weight gain Coarse, dry hair Hair loss Dry, rough skin Cold intolerance Muscle cramps Constipation Depression Irritability Memory loss Abnormal menstrual cycle Decreased libido Hypothalamus TRH Pituitary gland TSH gland FT4 Primary CRETINISM Congenital hypothyroidism 1 in 4000 live births Hypoplasia of thyroid gland Failure of gland to move to normal location Ineffective hormone (enzyme deficiency) CRETINISM Abnormal bone formation à stunted growth Mental retardation Pale, gray, cool skin Constipation Large tongue Poor muscle tone CRETINISM - TREATMENT hormone replacement Prevention: Screen at birth Improved prognosis is treatment started in first 2 months of life HASHIMOTO S DISEASE Most common thyroid disorder in U.S. Chronic lymphocytic thyroiditis or chronic autoimmune thyroiditis Affect 14 million people in U.S. Women more likely than men Middle-aged

7 HASHIMOTO S DISEASE - CAUSES Autoimmune disease Antibodies attack healthy thyroid tissue Leads to inflammation Decreased FT3 and FT4 Autoantibodies to TPO Decreased FT3 and FT4 COMPLICATIONS OF HASHIMOTO S Goiter (due to increased TSH) Increased risk of heart disease Depression Myxedema coma Severest form of hypothyroidism Mental slowing, profound lethargy, ultimately coma à life threatening TREATMENT FOR HASHIMOTO S Hormone replacement Levothyroxine (Synthroid) Dosage depends on degree of thyroid failure (range µg daily) and age Repeat TSH in ~6 weeks Change dosage (25-50 µg) as needed Take same time each day Takes 2-3 months for improvement in symptoms TREATMENT FOR HASHIMOTO S Adults older than 50 yr or those with heart disease: Start Levothyroxine 25 µg daily Adjust 25 µg every four weeks according to response, TSH levels, and angina symptoms TREATMENT FOR HASHIMOTO S Some patients do not feel completely well, despite normal TSH levels Need to bring TSH levels down to lower end of normal range Erratic TSH levels, despite constant dose of Levothyroxine Poor adherence Rule out malabsorption THYROID DISORDERS cancer Goiters nodules itis

HYPERTHYROIDISM CAUSES - PRIMARY HYPERTHYROIDISM Grave s disease most common Toxic nodular or multinodular goiter itis Pituitary tumor Secretes TSH Secondary hyperthyroidism 43 44 SYMPTOMS -

irregular cycle Increased bowel movements LAB EVALUATION Hypothalamus TRH Pituitary gland TSH gland FT4 Primary 45 46 GRAVE S DISEASE Accounts for ~75% hyperthyroidism Females 8x more likely than

8 HYPERTHYROIDISM CAUSES - PRIMARY HYPERTHYROIDISM Grave s disease most common Toxic nodular or multinodular goiter itis Pituitary tumor Secretes TSH Secondary hyperthyroidism SYMPTOMS - HYPERTHYROIDISM Fatigue Muscle weakness Weight loss Hand tremors Mood swings Anxiety Rapid heartbeat Irregular heartbeat or hear palpitations Dry skin Trouble sleeping Light menstrual flow or irregular cycle Increased bowel movements LAB EVALUATION Hypothalamus TRH Pituitary gland TSH gland FT4 Primary GRAVE S DISEASE Accounts for ~75% hyperthyroidism Females 8x more likely than males Typically occurs between ages of yr. Familial tendency GRAVE S DISEASE Autoimmune disease Presence of thyroid stimulating immunoglobin Binds to TSH receptors on thyroid gland Increased T3 and T4 Autoantibodies to TPO Decreased FT3 and FT

GRAVE S DISEASE Inflammation of tissues around eyes causing swelling Thickening of skin over lower legs Goiter sometimes present 49 50 TREATMENT FOR GRAVE S Beta-blockers

euthyroidism 2/3 patients relapse one year after treatment stops Younger patients less likely to enter remission Symptoms resolve slowly after treatment started TREATMENT FOR

Last resort if no response to treatment 51 52 THYROID STORM Life threatening emergency Rare Extremely high thyroid hormones Marked elevation in body temperature High mortality

9 GRAVE S DISEASE Inflammation of tissues around eyes causing swelling Thickening of skin over lower legs Goiter sometimes present TREATMENT FOR GRAVE S Beta-blockers (propranolol) treats symptoms in early treatment Anti-thyroid drugs Propylthiouracil (PTU) or methimazole Often add levothyroxine after 4 weeks of treatment to maintain euthyroidism 2/3 patients relapse one year after treatment stops Younger patients less likely to enter remission Symptoms resolve slowly after treatment started TREATMENT FOR GRAVE S Treat with radioiodine cell destruction ~90% patients with Grave s disease treated with single dose May cause hypothyroidism (40-60% patients within one year) ectomy Last resort if no response to treatment THYROID STORM Life threatening emergency Rare Extremely high thyroid hormones Marked elevation in body temperature High mortality rate (30%) THYROID STORM Usually caused by stress: Symptoms: Infection Trauma Surgery Delivery High fever Rapid heartbeat Disorientation Chest pain Shortness of breath Inc sweating weakness

THYROID STORM Prevention à Early treatment for hyperthyroidism Recognize warning signs & get treated immediately Highly elevated T3 & T4 Tachycardia TREATMENT FOR THYROID STORM Propylthiouracil large

10 THYROID STORM Prevention à Early treatment for hyperthyroidism Recognize warning signs & get treated immediately Highly elevated T3 & T4 Tachycardia TREATMENT FOR THYROID STORM Propylthiouracil large doses If heart failure à propranolol Glucocorticoids à inhibits conversion of T4 to T THYROID DISORDERS Goiters nodules itis cancer HOT NODULE Toxic nodular goiter or toxic adenoma Benign lumps on thyroid gland Excessive thyroid hormones Single hot nodule contains thyroid cells which have lost their regulatory mechanism that dictates amount of hormone to produce THYROID NODULES Nodule = abnormal overgrowth of tissue in thyroid gland May be solid or fluid filled Up to 50% of adults have at least one thyroid nodule Asymptomatic More common as people age Typically benign SYMPTOMS THYROID NODULES Rapidly growing lump on neck Lump felt in throat Difficulty swallowing Hoarseness Enlarged lymph nodes May have symptoms of hyperthyroidism

THYROID NODULES Elevated T3 and T4 Decreased TSH Treatment: Careful monitoring with ultrasound Anti-thyroid drugs in combination with beta blockers Radioiodine If malignant à surgical removal THYROID

11 THYROID NODULES Elevated T3 and T4 Decreased TSH Treatment: Careful monitoring with ultrasound Anti-thyroid drugs in combination with beta blockers Radioiodine If malignant à surgical removal THYROID DISORDERS Goiters cancer nodules itis THYROIDITIS ACUTE THYROIDITIS Inflammation of thyroid gland Can lead to excessive thyroid hormones Acute thyroiditis Caused by infection Postpartum thyroiditis 1 in 20 women Few months following delivery Rare Typically affects children or young adults Lab results: ESR WBC Normal thyroid function Symptoms: pain Small goiter Fever, dysphagia, erythema over thyroid Treatment: Antibiotics THYROID DISORDERS THYROID CANCER Goiters nodules itis 56,000 new cases/year in U.S. Females 3x more likely than males cancer Most commonly occurs after age of 30 yr. More aggressive in older patients

THYROID CANCER - SYMPTOMS Hoarse voice TYPES OF THYROID CANCER 3% 2% Neck pain Enlarged lymph nodes 15% Papillary/follicular Follicular/Hyrthle Medullary Anaplastic 80% 67 68 THYROID CANCER -

12 THYROID CANCER - SYMPTOMS Hoarse voice TYPES OF THYROID CANCER 3% 2% Neck pain Enlarged lymph nodes 15% Papillary/follicular Follicular/Hyrthle Medullary Anaplastic 80% THYROID CANCER - PROGNOSIS Most are curable 97% cure rate if treated appropriately Papillary & follicular Remove portion of thyroid gland that harbors cancer THYROID CANCER - PROGNOSIS Medullary thyroid cancer Tends to spread to lymph nodes More aggressive treatment needed Complete thyroid removal (plus local lymph nodes) Anaplastic thyroid cancer Incurable Very aggressive TREATMENT THYROID CANCER Radioactive iodine given after removal of thyroid Destroys any remaining thyroid cells Medullary cancer cant absorb iodine Treat only with surgery PITUITARY ADENOMA 71 12

13 PITUITARY ADENOMA Benign, slow-growing tumor on pituitary gland Relatively common 1 in 1000 adults Usually occurs spontaneously PITUITARY ADENOMA Either hormone-producing or hormoneinactivating tumors Hormone-producing adenomas: TSH-secreting pituitary adenoma Prolactin-secreting pituitary adenoma Growth hormone-secreting pituitary adenoma ACTH-secreting pituitary adenoma LAB EVALUATION Hypothalamus TRH Pituitary gland TSH gland FT4 Secondary CONFIRMATION OF THYROID DISEASE 75 WHAT IS GOING ON? Is the patient symptomatic? Does patient need treatment? Is the patient euthyroid? THYROID STIMULATING HORMONE Single most useful test in diagnosis of thyroid disease hstsh Detects TSH <0.001 mu/l Differentiates euthyroid, hyperthyroid, & hypothyroid

14 hstsh <0.1 mu/l mu/l Presumptive diagnosis Confirmatory testing Hyperthyroid suspected Confirm with FT4 or FT3 Borderline thyroid status Do FT4, FT3, or TRH stimulation mu/l No thyroid dysfunction No further testing >4.8 mu/l Hypothyroid suspected Confirm with FT4 TOTAL THYROXINE (TT 4 ) In circulation, 99.7% bound to proteins Detection of TT 4 : Bound T 4 released from protein in vitro and measured using chemiluminescence TT 4 may change depending on changes in TBG concentration Estrogen!! Replaced with FT TRIIODOTHYRONINE (T 3 ) Most active thyroid hormone Detection of TT 3 : Bound T 3 released from protein in vitro Helpful in confirmation of hyperthyroidism Often normal in hypothyroidism REVERSE T 3 (rt 3 ) Metabolite with minimal metabolic activity produced by T 4 Patient with NTI: T 3 rt 3 Serum T3 dec because enzyme that converts T4 to T3 is blocked Patient with hypothyroidism: T 3 rt Clinical condition T4 T3 rt3 FT4 TSH THYROID SCANNING Graves disease I I NA I D,U Multinodular goider I I NA I D,U Toxic adenoma I I NA I D,U Primary hypothyroidism Nonthyroid disease D D,N NA D I N,D N,D N,I N,I N Nuclear imaging Inject radioactive iodine Checks thyroid function or abnormalities (lumps, inflammation, cancer) Increased uptake à hyperthyroidism Decreased uptake à hypothyroidism I=increase, D=decrease, U=undetectable, NA=not applicable, N=normal

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Thyroid Disorders. January 2019

Thyroid Disorders. January 2019 Thyroid Disorders January 2019 What is the Thyroid? The thyroid is a small butterfly-shaped gland inside the neck, located in front of the trachea (windpipe) and below the larynx (voicebox). It produces